Genetic Variant SNAP25-AS1:n.133-19876T>A (chr20-10216813-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000421143.7(SNAP25-AS1):n.133-19876T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 151,468 control chromosomes in the GnomAD database, including 20,672 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.51 ( 20672 hom., cov: 29)

Consequence

SNAP25-AS1
ENST00000421143.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.26

Publications

9 publications found

Variant links:

Genes affected

SNAP25-AS1 (HGNC:44312): (SNAP25 antisense RNA 1)

SNAP25-AS1 links:

SNAP25 (HGNC:11132): (synaptosome associated protein 25) Synaptic vesicle membrane docking and fusion is mediated by SNAREs (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) located on the vesicle membrane (v-SNAREs) and the target membrane (t-SNAREs). The assembled v-SNARE/t-SNARE complex consists of a bundle of four helices, one of which is supplied by v-SNARE and the other three by t-SNARE. For t-SNAREs on the plasma membrane, the protein syntaxin supplies one helix and the protein encoded by this gene contributes the other two. Therefore, this gene product is a presynaptic plasma membrane protein involved in the regulation of neurotransmitter release. Two alternative transcript variants encoding different protein isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

SNAP25 Gene-Disease associations (from GenCC):

genetic developmental and epileptic encephalopathy
Inheritance: AD Classification: DEFINITIVE, MODERATE Submitted by: Ambry Genetics, ClinGen
congenital myasthenic syndrome 18
Inheritance: AD Classification: STRONG, LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)
presynaptic congenital myasthenic syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

SNAP25 links:

ENSG00000305058 (HGNC:):

ENSG00000305058 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNAP25-AS1	NR_040710.1 link	n.270+2424T>A		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
SNAP25-AS1	ENST00000421143.7 link	n.133-19876T>A	intron_variant	Intron 1 of 3	5
SNAP25-AS1	ENST00000426491.5 link	n.270+2424T>A	intron_variant	Intron 1 of 4	5
SNAP25-AS1	ENST00000451151.7 link	n.301+2424T>A	intron_variant	Intron 1 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.513

AC:

77711

AN:

151350

Hom.:

20663

Cov.:

show subpopulations

Gnomad AFR

AF:

0.353

Gnomad AMI

AF:

0.553

Gnomad AMR

AF:

0.631

Gnomad ASJ

AF:

0.620

Gnomad EAS

AF:

0.519

Gnomad SAS

AF:

0.540

Gnomad FIN

AF:

0.583

Gnomad MID

AF:

0.576

Gnomad NFE

AF:

0.564

Gnomad OTH

AF:

0.559

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.513

AC:

77745

AN:

151468

Hom.:

20672

Cov.:

AF XY:

0.518

AC XY:

38304

AN XY:

73966

show subpopulations

African (AFR)

AF:

0.353

AC:

14538

AN:

41234

American (AMR)

AF:

0.631

AC:

9606

AN:

15214

Ashkenazi Jewish (ASJ)

AF:

0.620

AC:

2151

AN:

3468

East Asian (EAS)

AF:

0.520

AC:

2666

AN:

5128

South Asian (SAS)

AF:

0.539

AC:

2577

AN:

4784

European-Finnish (FIN)

AF:

0.583

AC:

6087

AN:

10440

Middle Eastern (MID)

AF:

0.582

AC:

171

AN:

294

European-Non Finnish (NFE)

AF:

0.564

AC:

38268

AN:

67894

Other (OTH)

AF:

0.560

AC:

1181

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1804

3607

5411

7214

9018

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

692

1384

2076

2768

3460

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.530

Hom.:

2714

Bravo

AF:

0.513

Asia WGS

AF:

0.542

AC:

1883

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

6.8

(source)

DANN

Benign

0.79

PhyloP100

1.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over